Magnetic flux density based DNA sequencing

ABSTRACT

In an approach to magnetic flux density based DNA sequencing, a static magnetic field is provided. A chain of nucleotides is passed through the magnetic field. A change in magnetic flux density of the static magnetic field due to an ionic voltage associated with an individual nucleotide or base pair of the chain of nucleotides is measured. An identity of the nucleotide is determined based on the change in magnetic flux density.

BACKGROUND

The present disclosure relates generally to the field of genomic (DNA)computing, and more particularly to methods for DNA sequencing.

DNA computing is a rapidly evolving interdisciplinary field combiningbiochemistry and molecular biology with computational theory to solveproblems. DNA computing leverages properties of DNA to determine answersto problems encoded in DNA strands in a massively parallel fashion.

DNA sequencing is an integral part of modern DNA computing techniques.Sequences for thousands of organisms have been decoded and stored indatabases, and in turn used in various fields such as machine learning,genomic medicine, and so forth.

Conventional methods and tools for DNA sequencing include, for examplebut without limitation, primer extension using a DNA polymerase, directblotting electrophoresis, radioactive defective nucleotides, SDS-PAGEelectrophoresis, Maxam-Gilbet sequencing, ion torrent semiconductorsequencing, and tunneling current DNA sequencing.

Current research is mainly focused on nanopore sequencing usingtunneling currents, which allows for faster and more accurate results. Ananopore-based device provides single-molecule detection based onelectrophoretically driving DNA molecules (i.e., their nucleotides,adenine, cytosine, guanine, and thymine) in solution through anano-scale pore. Nucleotides are identified based on ionic conductancevariation due to the movement of nucleotides in an electrochemicalcircuit.

SUMMARY

A method for magnetic flux density based DNA sequencing includesproviding a static magnetic field. A chain of nucleotides is passedthrough the magnetic field. A change in magnetic flux density of thestatic magnetic field due to an ionic voltage associated with anindividual nucleotide or base pair of the chain of nucleotides ismeasured. An identity of the nucleotide is determined based on thechange in magnetic flux density.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a flowchart depicting a method for magnetic flux density basedDNA sequencing, in accordance with at least one embodiment of thepresent invention;

FIG. 2A is a diagram of a passing operation for single-strandednucleotides, for an embodiment of the method of FIG. 1;

FIG. 2B is a diagram of a passing operation for double-strandednucleotides, for an embodiment of the method of FIG. 1;

FIG. 3 is table of ionization potential values for individualnucleotides and base pairs, respectively, used in a determiningoperation, for an embodiment of the method of FIG. 1;

FIG. 4 is a diagram of the relationship between magnetic field,displacement, charge, and velocity used in a determining operation, foran embodiment of the method of FIG. 1; and

FIG. 5 is a diagram of a passing operation for single-strandednucleotides, in accordance with conventional technology.

DETAILED DESCRIPTION

Embodiments described herein enable DNA sequencing based on measuring achange in magnetic flux density as nucleotides are passed through astatic magnetic field.

It should be noted that references throughout this specification tofeatures, advantages, or similar language herein do not imply that allof the features and advantages that may be realized with the embodimentsdisclosed herein should be, or are in, any single embodiment of theinvention. Rather, language referring to the features and advantages isunderstood to mean that a specific feature, advantage, or characteristicdescribed in connection with an embodiment is included in at least oneembodiment of the present invention. Thus, discussion of the features,advantages, and similar language, throughout this specification may, butdo not necessarily, refer to the same embodiment.

Furthermore, the described features, advantages, and characteristics ofthe invention may be combined in any suitable manner in one or moreembodiments. One skilled in the relevant art will recognize that theinvention may be practiced without one or more of the specific featuresor advantages of a particular embodiment. In other instances, additionalfeatures and advantages may be recognized in certain embodiments thatmay not be present in all embodiments of the invention.

These features and advantages will become more fully apparent from thefollowing drawings, description and appended claims, or may be learnedby the practice of the invention as set forth hereinafter.

The scope of the present invention is to be determined by the claims.Accordingly, any features, characteristics, advantages, or the like,discussed below in the discussion of embodiments of this specificationshall not be taken to mean that such features, characteristics,advantages, or the like are required to practice the present inventionas defined by the claims.

Embodiments of the present invention are described with reference to theFigures. FIG. 1 is a flowchart depicting an embodiment of a method 100for magnetic flux density based DNA sequencing. As depicted, method 100includes providing (105) a static magnetic field; passing (110) a chainof nucleotides through the magnetic field; measuring (115) a change inmagnetic flux density; and determining (120) an identity of a nucleotidebased on the change in magnetic flux density.

Providing (105) a static magnetic field may include using anelectromagnet and coil of wire to produce a magnetic field. In anothernon-limiting embodiment, a static magnetic field may be produced usingpermanent magnets.

Passing (110) a chain of nucleotides through the magnetic field mayinclude passing single or paired nucleotides through a nanopore. Onlyone nucleotide, or one pair of nucleotides (or “base pair”), dependingon the device setup, should be passed through the magnetic field at atime in order to avoid false results. Movement of the nucleotides occursbecause of the charges carried by the nucleotides in the magnetic field.Additional details of passing operation 110 are disclosed herein withreference to FIG. 2A-B.

Measuring (115) a change in magnetic flux density may include using ahigh-precision magnetometer to measure a change in the magnetic fluxdensity of the magnetic field due to an ionic voltage associated with anindividual nucleotide of the chain of nucleotides. For example, themagnetometer can be used to detect magnetic field changes at regularintervals based on the velocity of the nucleotides moving through thenanopore and magnetic field. The type of magnetometer used in measuringoperation 115 should be selected based on ability to detect smallchanges in magnetic field with high accuracy. Measurements may be takenat any point within the magnetic field, e.g., in close proximity to thenanopore.

Determining (120) an identity of a nucleotide based on the change inmagnetic flux density may include applying the Biot-Savart law to thechange, where the Biot-Savart law describes a magnetic field generatedby an electric current in terms of magnitude, direction, length, andproximity of the current. Additional details of determining operation120 are disclosed herein with reference to FIGS. 3 and 4.

As shown in diagram 200 (FIG. 2A), a single chain 202 of nucleotides maybe passed through a nanopore 204 in plate 206, in a static magneticfield 208.

As shown in diagram 250 (FIG. 2B), the device setup can be altered toaccommodate passage of a double strand 252 of nucleotides throughnanopore 254 in plate 256, in static magnetic field 258. Magnetic field258 can be adjusted to ensure that only one base pair passes through thefield at a time.

As shown in table 300 (FIG. 3), individual nucleotides and pairs ofnucleotides are associated with respective and identifying ionizationpotentials. The differences in ionization potential are based on thefact that each nucleotide (i.e., adenine, cytosine, guanine, thymine) orcombination of nucleotides differs in features such as number of C, H,O, and N atoms; number of hydrogen bonds; number of free electrons;polarity; and bond length.

As shown in diagram 400 (FIG. 4), a relationship between magnetic field402, displacement 404, point charge 406, and velocity 408 can beleveraged for nucleotide identification in determining operation 120.Displacement 404 of point charge 406 at velocity 408 through magneticfield 402 causes a deflection of magnetic field 402.

The Biot-Savart law can be applied to the deflection illustrated bydiagram 400 in order to identify an individual nucleotide or pair ofnucleotides. For example, the Biot-Savart law for a point charge can beapplied to a point charge 406 moving at a constant velocity 408according to the following relationships, wherein μ_(o) is thepermeability constant, q is the magnitude of point charge 406, andboldface type is used to represent a vector quantity:

$B = {\frac{\mu_{0}}{4\pi}\frac{qvr}{r^{3}}}$${B} = {\frac{\mu_{0}}{4\pi}\frac{{qv}\;\sin\;\theta}{r^{2}}}$

Velocity 408 of the chain of nucleotides in a gel medium is affected byvoltage, concentration of the gel, composition of the gel, and size ofthe chain. A constant velocity 408 can be achieved if these factors arekept constant throughout passing operation 110 and measuring operation115.

Respective theoretical changes in magnetic flux density may beassociated with each nucleotide and base pair based on the aboveparameters (e.g., velocity 408, θ, r). Actual changes observed inmeasuring operation 115 can be plotted in order to identify nucleotidesand base pairs that produced a deflection matching a theoretical value.

In addition to the steps and operations disclosed herein, additionalsteps and operations may be performed while retaining the spirit andintent of the disclosed embodiments. Operations of method 100 mayproduce data that is used in turn for machine learning, predictiveanalytics, and other DNA computing applications. In one of many possibleexamples, the information in DNA as revealed through DNA sequencingmethods can be used in research seeking personalized cancer treatments.

Diagram 500 (FIG. 5) illustrates an example of DNA sequencing based onconventional methods. Diagram 500 shows a single strand 502 ofnucleotides passed through nanopore 504 in plate 506 and a tunnelingcurrent 508 between electrodes 510.

Embodiments of the present invention may recognize one or more of thefollowing facts, potential problems and/or potential areas forimprovement with respect to conventional methods for nanopore sequencingusing tunneling currents: (i) the gap between the electrodes should besmall, in the order of nanometers, to allow only a single chain ofnucleotides to pass through, so 2-3 nucleotides of DNA may contribute tothe ionic current blockade, resulting in greater than expectedresistance and, in turn, false results; (ii) experimental device setupmust be altered to allow a chain of complementary base pairs (as opposedto unpaired nucleotides) to pass through, increasing the cost of theinfrastructure; and/or (iii) the flow of tunneling current through asingle nucleotide alters the bonding structure of the nucleotide,affecting stability.

Embodiments of the present invention may include one or more of thefollowing features, characteristics, and/or advantages: (i) the devicesetup can be used for identifying sequences for both single anddouble-stranded DNA without additional infrastructure, making the setupinexpensive in comparison with conventional methods; (ii) device set-upis simple in comparison with conventional methods, requiring only asingle electromagnet and coil of wire to provide a magnetic field; (iii)high-precision magnetometers can be used to measure change in magneticflux density quickly and with low noise increasing usefulness foradvanced analytics and machine learning applications; (iv)high-precision magnetometers can be used to measure magnetic changeseven at the atomic level; and/or (v) because there is no flow ofelectric current (as in the case of tunneling based sequencing), longsequence readouts are possible without change in the structure of theDNA pairs or kinetics of the ecosystem.

It should be noted that this description is not intended to limit theinvention. On the contrary, the embodiments presented are intended tocover some of the alternatives, modifications, and equivalents, whichare included in the spirit and scope of the invention as defined by theappended claims. Further, in the detailed description of the disclosedembodiments, numerous specific details are set forth in order to providea comprehensive understanding of the claimed invention. However, oneskilled in the art would understand that various embodiments may bepracticed without such specific details.

Although the features and elements of the embodiments disclosed hereinare described in particular combinations, each feature or element can beused alone without the other features and elements of the embodiments orin various combinations with or without other features and elementsdisclosed herein.

This written description uses examples of the subject matter disclosedto enable any person skilled in the art to practice the same, includingmaking and using any devices or systems and performing any incorporatedmethods. The patentable scope of the subject matter is defined by theclaims, and may include other examples that occur to those skilled inthe art. Such other examples are intended to be within the scope of theclaims.

What is claimed is:
 1. A method for magnetic flux density based DNAsequencing, the method comprising: providing a static magnetic field;passing a chain of nucleotides through the static magnetic field;measuring a change in magnetic flux density of the static magnetic fielddue to an ionic voltage associated with an individual nucleotide or basepair of the chain of nucleotides; and determining an identity of theindividual nucleotide or the base pair of the chain of nucleotides basedon the change in magnetic flux density.
 2. The method of claim 1,wherein providing a static magnetic field further comprises: generatinga static magnetic field using permanent magnets or a singleelectromagnet associated with a coil of wire.
 3. The method of claim 1,wherein passing a chain of nucleotides through the static magnetic fieldfurther comprises: passing the chain of nucleotides through a nanoporedevice and a gel medium.
 4. The method of claim 1, wherein the chain ofnucleotides comprises a single strand of nucleotides.
 5. The method ofclaim 1, wherein the chain of nucleotides comprises double-strandednucleotides.
 6. The method of claim 1, wherein measuring a change inmagnetic flux density of the static magnetic field further comprises:measuring magnetic field changes using a high precision magnetometer. 7.The method of claim 6, wherein the magnetometer detects magnetic fieldchanges at predefined intervals based on a velocity of the chain ofnucleotides.
 8. The method of claim 1, wherein determining an identityof the nucleotide further comprises: applying the Biot-Savart law for apoint charge to a deflection of the static magnetic field.